高成炎臺灣大學：資訊工程學研究所陳權忠Chen, Chiuan-JungChiuan-JungChen2007-11-262018-07-052007-11-262018-07-052004http://ntur.lib.ntu.edu.tw//handle/246246/53695A major limitation of current comparative modeling method is the accuracy with which regions that are structurally divergent from homologues of known structure can be modeled, and we call this kind of problem loop modeling problem. There are two difficulties of loop modeling problem; the first one is how to generate a feasible conformation of loop, and the other is to find the closest conformation to the native one. Here we present a method which combine several algorithm to solve these two difficulties describing above. For the first problem, we adopt an algorithm called CCD (Cyclic Coordinate Descent), which iteratively change the phi and phi angles from the start residue to the end residue to make the conformation close. And the other one, we use a simple energy function to evaluate the stability of a given loop conformation, and the search algorithm FCEA to find the lowest energy conformation from the random building conformations. We evaluate this method by predict a test set of 14 loops, and the final RMSD of them are almost between 0.72Å~2.81 Å.Chapter 1 Introduction 1 1.1 Motivation 1 Ab initio approach： 2 Database Approach： 3 1.2 Overview 4 Chapter 2 Cyclic Coordinate Descent 6 2.1 Introduction 6 2.2 Overview 7 2.3 Minimize Squared Distances 9 2.4 The ability of CCD 11 Chapter 3 The Family Competition Evolutionary Approach 13 3.1 Introduction 13 3.2 Overview 13 3.3 Family Competition 15 3.4 Chromosome Representation 17 3.5 Recombination Operators 18 Modified Discrete Recombination： 18 BLX-0.5 and Intermediate Recombination： 18 3.6 Mutation Operators 19 Self-Adaptive Gaussian Mutation： 20 Self-Adaptive Cauchy Mutation： 20 Decreasing-based Gaussian Mutation： 22 3.7 Adaptive Rules 23 A-decrease-rule： 23 D-increase-rule： 23 Chapter 4 A New Combinatorial loop modeling algorithm 24 4.1 Overview 24 4.2 Construct Backbone Conformation 25 4.3 FCCD：The combinatorial algorithm of FCEA and CCD 25 4.3.1 Chromosome Representation： 27 4.3.2 Offspring： 27 4.3.3 CCD： 28 4.4 Side-Chain Prediction with Rotamer Library 28 4.5 Energy function 30 Chapter 5 Conclusions 33 5.1 Test Set 33 5.2 Energy Function vs. RMSD 33 5.3 The Search ability of FCCD 36 5.4 result 38 5.5 Discussion and Future works 40 reference 42 Appendix A 45997179 bytesapplication/pdfen-US蛋白質迴圈結構structure predictionProtein Loopthesishttp://ntur.lib.ntu.edu.tw/bitstream/246246/53695/1/ntu-93-R90922084-1.pdf